4 below is another way of looking at these same concepts.ĪUC (area-under-the-curve): This is the overall amount of drug in the bloodstream after a dose. For AUC measurements, blood levels are usually collected every hour or so. Since the time 0 level is about equal to the time 12 level, the patient is at steady state. In this representation, the patient took the dose at time 0 and would be due for another dose at time 12 (hours). Please refer to Figures 3 and 4 for a picture of what all these PK measurements represent.Ībove are blood levels (Y-axis) of a drug over time (X-axis) after a patient takes a single dose. The following is a summary of these PK measurements and what they mean. There are certain terms and tests that researchers or doctors use when they study PK. In these people, the blood level of some drugs may build to very high levels if the drug dose is not reduced (see Figure 1: Drug Metabolism Pathways). Sometimes people have some kidney or liver illness. Drug elimination: This is how the body gets the drug out - usually by passing the drug into the urine (via the kidneys) or stool (via the liver). But, for other drugs that are metabolized by CYP3A4, like cholesterol drugs or erectile dysfunction drugs, Norvir and protease inhibitors may cause undesirable increases in blood concentrations (see Protease Inhibitor article). For the protease inhibitors that are boosted by Norvir, the higher blood levels may help the "boosted" drug work better. Norvir strongly inhibits CYP3A4 and causes most of the other protease inhibitors to build up in the blood. For example, CYP3A4 is probably the most important drug metabolizing enzyme because it metabolizes the most drugs, including protease inhibitors. Note that drugs can be listed as both an inducer and inhibitor and with multiple enzymes.Įach CYP has a different ability to metabolize a given chemical or drug. Arrows point to the various antiretrovirals and the general affect(s) that medicine has on that enzyme. CYP3A4, shown at the top of the pyramid and largest single part of the pyramid, is very important. Pyramid depicts the various CYP 450 enzymes in the body and the drug interactions with antiretrovirals. (Note how the 450 is dropped, but the CYP remains.)
Some examples of this are CYP1A2, CYP2D6, CYP3A4, etc. To distinguish one family from another, a letter and number are added to CYP (again, dropping the 450 numbering). Within the CYP-450 system, though, there are different enzyme families. When doctors and pharmacists talk about the CYP-450 system, they often just refer to the system as CYP and drop the 450 part. The CYP-450 enzymes are broken into three families (CYP1, CYP2 and CYP3) (see Figure 2: Antiretrovirals and CYP-450 Isoenzymes). CYP-450 enzymes are mostly in the intestines and liver. The CYP-450 (pronounced "sip") enzyme system is a well-known group of human enzymes that metabolize drugs and chemicals in the body. On the other hand, a drug can also speed up the metabolism of another drug (called induction). A lot of drug-drug interactions happen because one drug interferes with the metabolism of another drug (called inhibition). Metabolism involves breaking a drug down or adding a chemical that makes it easier to pass it into urine or stool. Drug metabolism: This is how the body chemically changes a drug - usually in the intestines and liver.